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Ethical and Scientific Issues

in the use of Human Stem Cells


Allen R. Dyer, M.D., Ph.D.

dyer@etsu.edu

http://faculty.etsu.edu/dyer

Legal

Scientific

Religious

Ethical

Legal

Scientific

Religious

Ethical

Principles of Bioethics


Beneficence (or Paternalism)


Physician
-
centered decisions


Non
-
maleficence


First Do No Harm


Autonomy


Patient’s right to self
-


determination


Justice


Fairness

Ethical

Evolution of Ethical Priorities

1950s
-
1960s

1970s
-
1980s


1990s


2000+

Beneficenc
e

Autonomy




Justice

Autonomy

Beneficence

Social
justice

Social
justice

Autonomy

Beneficence

Social control

Autonomy

Beneficence

Allen R. Dyer: Ethics of Human Genetic Intervention

Experimental Neurology

144,168
-
172 (1997)

Human Genetic Intervention

Somatic cells

Germ
-
line

Cure or
prevention of
disease


Gene therapy


Genetic
Engineering

Enhancement
of capabilities


Genetic
Engineering


Genetic
Engineering

Allen R. Dyer: Ethics of Human Genetic Intervention

Experimental Neurology

144,168
-
172 (1997)

Ethical Issues for Gene Therapy
and Genetic Engineering


Safety (nonmaleficence)


Efficacy (beneficence)


Informed consent (autonomy)


Allocation of resources (justice)

Allen R. Dyer: Ethics of Human Genetic Intervention

Experimental Neurology

144,168
-
172 (1997)

Ethical issues in assisted
reproduction


“Ethics, Advertising and Assisted Reproduction:

The Goals and Methods of Advertising”


Concern for “commodification” of life and life
products


Concern for availability, allocation, and pricing

of the technology

Allen R. Dyer:
Women’s Health Issues

7:3,

pp. 143
-
148. May/June 1997

Human Embryo

Blastocyst stage Immunosurgery Embryonic stem cells

Scientific


STEM CELL (DEFINITION)

A cell that has the ability to continuously

divide and differentiate (develop)

into various other kind(s) of cells/tissues


Stem cell type

Description

Examples

Totipotent

Each cell can develop into a new
individual

Cells from early (1
-
3
days) embryos

Pluripotent

Cells can form any (over 200)
cell types

Some cells of blastocyst
(5 to 14 days)

Multipotent

Cells differentiated, but can form
a number of other tissues

Fetal tissue, cord blood,
and adult stem cells


In 1968, the first bone marrow transplant was


successfully used in treatment of SCID



Since the 1970’s, bone marrow transplants have been


used for treatment of immunodeficiencies


and leukemias


History of Human Stem Cell
Research


Bone Marrow Stem Cells

History of Human Embryonic


Stem Cell Research



1954


John Enders received a

Nobel prize in Medicine for growing

polio virus in human embryonic

kidney cells


History of Human Embryonic

Stem Cell Research


In 1998, James Thomson (University of Wisconsin
-
Madison) isolated cells from the inner cell mass of the early
embryo, and developed the first human embryonic stem cell
lines.



In 1998, John Gearhart (Johns Hopkins University)

derived human embryonic germ cells from cells in fetal
gonadal tissue (primordial germ cells).


Pluripotent stem cell “lines” were developed

from both sources


History of Somatic Cell
Nuclear Transfer (Cloning)


1952


Briggs and King cloned tadpoles


1996


The first mammal cloned from adult


cells was Dolly, the sheep.


1998


Mice cloned


1998


Cows cloned


2000
-

Pigs cloned


2001
-

Cat cloned (CC = Carbon copy)


2002
-

Rabbits cloned


2004
-

Human Embryos cloned and


embryonic stem cells extracted



2004
--

Bull serially cloned


Possible Uses of


Stem Cell Technology


Replaceable tissues/organs


Repair of defective cell types


Delivery of genetic therapies


Delivery of chemotherapeutic agents


Diseases potentially treatable
with stem cells

Cancer

Diabetes

Parkinson's

Alzheimer’s

Spinal Cord injury

Heart Disease

Infertility


Basic knowledge

of cell development

Who are stakeholders?

People with illnesses

Parents of children with illnesses

Physicians and scientists

Research Institutes: NIH, Universities,

Corporations and shareholders (those who might profit)

Government (s)


USA, California, UK, Australia, Czech Republic,


South Korea

Taxpayers

Churches and clergy

The cells themselves


Misconceptions hamper
understanding

Sources of stem cells:




Adult stem cells:



bone marrow, blood, muscle, fat, nerves , etc.



Umbilical cord stem cells:



Umbilical cord blood and placenta



Embryonic stem cells:



From TABs or (supernumerary) IVFs


Embryos made solely for research purposes


Embryos made using somatic cell nuclear transfer (SCNT)




DNA

Possible points of contention


Source of cells


Source of funding


Autonomy or freedom


Respect for life


Definition of “life”


Legal Considerations:

Embryonic Stem Cell Research


1973


moratorium on government

financing for human embryo research


1988


NIH Panel voted 19
-
2 in

favor of government funding


1989


DHHS Secretary Sullivan

extended the moratorium


Legal

Legal Issues:

Embryonic Stem Cell Research


1990


Congress voted to override the


moratorium, vetoed by President


George H.W. Bush


1993


President Clinton lifted the ban


1994


the Human Embryo Research


Panel favored research, but Clinton


overrode the panel


1995


Congress banned federal funding


Legal Consideration:

Embryonic Stem Cell Research


August 25, 2000, President Clinton


allowed funding of research based

on cells from (aborted) human

fetal lines, but not embryonic cells


On August 9, 2001, President Bush

announced his decision to allow


Federal funds to be used only for


research on existing human

embryonic stem cell lines

created prior to his announcement

Laws Banning
Reproductive

Cloning

Laws Banning
Research

Cloning

Embryonic
Research

Cloning Laws Worldwide

Legislation on Reproductive/Therapeutic
Cloning, Embryo Research,

and Stem Cell Research 2003

Reproductive Cloning allowed

None

Therapeutic Cloning (SCNT) allowed

(US, UK, Netherlands, Japan, Israel)

5

(General) Research on Embryos allowed

+Australia, Brazil, Canada, Finland,
France, Iceland, Spain, Sweden

13

Stem Cell Research on Spare Embryos
allowed

12

Source:
Encyclopedia of Bioethics

Allow for the procurement of human
embryonic cells from supernumerary
embryos by law


Finland


Greece


The Netherlands


Sweden


United Kingdom

Prohibit procurement but allow by law the import


and use of human embryonic stem cell lines

Germany

IVF cells only to be used for
medical assisted reproduction


Austria


Denmark


France


Iceland


Spain

Allowing for creation of human embryos


for stem cell procurement by law

United Kingdom

The Case for Federal Funding

“The only possible source for adequate support of
our medical schools and medical research is the
taxing power of the Federal Government.

Such a program must assure complete freedom for
the institutions and the individual scientists in
developing and conducting their research work.”



a)
1932

b)
1945

c)
1995

d)
2004


The Case for Federal Funding

“The only possible source for adequate support of
our medical schools and medical research is the
taxing power of the Federal Government.

Such a program must assure complete freedom for
the institutions and the individual scientists in
developing and conducting their research work.”



b) 1945
US Surgeon General Thomas Parran arguing for
the establishment of the National Institutes of Health
(NIH)


California Stem Cell Research
and Cures Initiative


November, 2004, ballot initiative passed


Run by an Independent Citizen’s
Oversight Committee composed of
politicians, advocacy groups, and
executive officers of universities


Provides $3 billion for embryonic stem cell
research


Grants up to $6 million


Includes construction costs

Contributions from

Religious traditions

(No consistent positions)


Catholic (varies over time) tends to identify point
of life at conception


Protestant: varies by denomination, region,
congregation, and parishioner


Jewish tends to favor research, early
intervention, prenatal diagnosis, and treatment


Muslim tends toward pragmatism in particular
context, e.g. goals of marriage, procreation


Buddhist many considerations and
interpretations.

Religious

Early Judaism



Genesis 1:28 “Be fruitful and increase in
number.”


Exodus 21: “When men strive together,
and hurt a woman with child, so that there
is a miscarriage, the one who hurt her
shall be fined. If harm follows, then you
shall give life for life.


Developing life not give legal status of a
person.


Abortion not condoned in early Judaism.

Early Christianity


New Testament takes no position on
abortion or the status of embryonic or fetal
life.


Negative references to
pharmakeia

may
refer to abortifacient drugs and not
medicine generally.


In translating Exodus from Hebrew to
Greek, “harm” become “form”.

Catholicism


The soul not joined to the body until
formation.


Only when fetal development advances to
a stage that resembles human form is it
possible for the human soul to be present.


40 days after conception for males/90 for
females.


Until 1869 Catholic Church recognized a
distinction between the ensouled and
unensouled fetus.

Another distinction


Possible
persons
-

entities that could possibly
develop into persons if certain actions were
taken with respect to them (e.g. implantation)


Potential

persons
-

entities that will develop into
persons in the normal course of events unless
that development is interrupted


Development of “primitive streak” at 14 days a
possible “moral marker”


Development of gastrulation, organ formation, at
17 days


Development of neural tube at 21 days

Protestant


Many forms


Luther and Calvin rejected the philosophical
theology of Thomas Aquinas


Protestantism sees abortion (and other reproductive
decisions) as a matter of individual conscience (no
papal authority)


now more tolerant of abortion as a matter of choice or
individual responsibility (no state religion).


Discouraged for less than urgent reasons

Contemporary Judaism


Tolerant of contemporary public policy of
“choice”


Teaches abortion should be chosen



only for compelling reasons.


Embryo’s status for the first forty days



(according to Talmud)


“as if it were simply water”.


Hence Judaism supportive of IVF and


Pre
-
implantation Genetic Diagnosis (PGD).


Islam


Koran 23:12
-
16 Human creation begins
with a tiny drop from which the larger fetus
is fashioned by God the creator, who
breathes life into what is formed.


Distinguishes between souled and
unensouled fetus.


End of 4th month
-
point when abortion is
no longer permissible.


Technology not valued abstractly:
reproductive technology must serve health
within context of marriage.

Asian Traditions


More practical and less divisive than in
West


Require woman to make thoughtful and
compassionate decisions


In Japan fetal loss is mourned and
observed with ritual and remembrance
(
mizuko
)


In China, abortion not only permitted but
mandatory after first child.


India, as China, has development stem
cell lines. Public encouragement for
potential benefit.


Buddhist Ethics

"Cloning is a different way of thinking
about the recycling of life,”



"It's a Buddhist way of thinking.”



Professor Yong Moon



from Korea's Seoul National University
at the American Association for the
Advancement of Science 2004


Just a few days earlier at the same
conference, Moon was part of the team
that announced it had successfully
cloned human embryos and extracted
sought
-
after and versatile embryonic
stem cells.


*Hwang, W.S., et al. 2004. Evidence of a
Pluripotent Human Embryonic Stem Cell Line
Derived from a Cloned Blastocyst.
Science

303:
1669
-
1674.



Confucian tradition




“Ren” = “good birth”


Chinese generally have a concern to reduce the
number of deleterious genetic diseases In the
population.


Collective good generally given higher priority
than that of the embryo or individual rights.



Cloned Embryos


Catholicism opposes ablation of inner cell mass
(ICM) of blastocyst.


Southern Baptist Convention (1999) vigorously
opposition to destruction of innocent human life
(including embryos)


Presbyterian Church (USA) (2001) “We affirm
the use of human stem cell tissue for research
that may result in the restoring of health to
those suffering from serious illness.”


Judaism stresses God
-
given human role in
mending creation. “The Torah commands us to
treat and cure the ill and to defeat disease
wherever possible.” (2002)


Ethical principles for
Embryonic Stem Cell
Research


Principle of
Respect



Embryo is human life which should not be damaged without
reason and good cause.


Because of potential benefit in treating human diseases,
research should be allowed and supported.


Principle of
Informed consent

(autonomy)


Principle of
Safety and utility

(non
-
malfeasance)


Principle of
Non
-
commercialization

(justice)


Tissues and cells should be donated


Buying and selling of gametes, embryos and fetal tissues
should not be allowed.

Preimplantation Genetic Diagnosis

P.G.D.

PGD

Cancer (Colon and Breast)

Cystic fibrosis

Cycle cell anemia

Ankylosing spondylosis

Huntington’s disease


Partial Birth Abortion


Currently under consideration by US Supreme Court

Challenges constitutionality of Partial
-
Birth Abortion Act of
November 2003. (Nebraska law struck down in 2000)



Fails to provide
an exception for procedures preformed to
protect the health of the pregnant woman.



Vaguely written



Places undue burden on women seeking abortion.



Supporters of the law argued that procedure was never
medically necessary.



Partial
-
birth abortion


With the ban, Congress targeted an abortion procedure,
known medically as "intact dilation and extraction," that
involves the partial delivery of a fetus. The skull is then
punctured and its contents evacuated to make it easier for
the head to pass through the birth canal. Doctors say it is
used only in exceedingly rare circumstances (1 in 500).



American College of Obstetricians and Gynecologists

has
said that the procedures banned under the measure
--

called
"intact dilation and extraction and evacuation" and "dilation
and extraction” (D & X)
--

are increasingly regarded as the
safest abortion procedures during the second trimester of
pregnancy.



Partial
-
birth abortion

Constitutional issues:

Right to privacy

Right to life (and definition of life)


“Child” or “Fetus”

Interest of the state

Freedom of religion

Legal versus moral considerations

Responsibility to make moral choices


Principles of Bioethics


Beneficence


Physician
-
centered decisions


Non
-
maleficence


First Do No Harm


Autonomy


Patient’s right to self
-


determination


Justice


Fairness

Ethical

Conclusion

The religions today, even in their disagreements,
serve to focus both our awe at the mysteries of our
humanity and our anxieties about our futures.
Religious traditions will probably continue to adapt
to our changing knowledge of ourselves and our
growing powers to modify our nature. In so doing
they will perhaps shed some light on our biological
origins and on our technological destiny.






Ronald Cole
-
Turner




Encyclopedia of Bioethics

Your role in 21st century
medicine

There are still many unanswered questions:


As physicians, you will be concerned with the particular details of
your patients’ lives.


You will face situations in which there will inevitably be
uncomfortable choices.


You will hope to be able to make those decisions with your patients
and for your patients best interests.


You will hope to be able to practice with in a legal environment
that respects science, knowledge, your training, and your own
moral convictions.